Porous materials play a significant role in a wide variety of industrial applications including processing, e.g. filtering, packaging, containing, and transporting manufactured goods and raw materials. The industrial settings in which they are used include the pharmaceutical and biotechnology industries; the oil and gas industries and the food processing and packaging industries, to name but a few.
In several of these industries such as the pharmaceutical and biotechnology industries and the food processing industry porous materials, e.g. membranes, may be used as filtration devices to eliminate undesirable and potentially harmful contaminants from marketable end products. Quality control and quality assurance requires that these filtration devices comply with desired performance criteria. Integrity testing provides a means for ensuring that a particular device meets its desired performance criteria. Typically, in the case of membranes, integrity testing ensures that the membrane is free of defects, e.g. breaches in the membrane exceeding a desired size limitation, which would impair the membrane function and thus allow the end product to become contaminated with harmful or undesirable material.
A variety of integrity tests suitable for ensuring the performance criteria of membranes, e.g., filtration devices, have been previously described. These include the particle challenge test, the liquid-liquid porometry test, bubble point test, the air-water diffusion test and diffusion tests measuring tracer components (see, e.g., U.S. Pat. Nos. 6,983,505; 6,568,282; 5,457,986; 5,282,380; 5,581,017; Phillips and DiLeo, 1996, Biologicals 24:243; Knight and Badenhop, 1990, 8th Annual Membrane Planning Conference, Newton, Mass.; Badenhop; Meltzer and Jorritz, 1998, Filtration in the Biopharmaceutical Industry, Marcel Dekkar, Inc., New York, N.Y.). A number of devices suitable for testing the integrity of a membrane have also been described (see, e.g., U.S. Pat. Nos. 4,701,861; 6,907,770; 4,881,176).
The previously described integrity tests have significant shortcomings. The particle challenge test, for example, is destructive and thus can only be performed once on a given specimen. Although it can be used for post-use integrity testing, it is not suitable for pre-use validation, except for validating the performance of a production lot. Lot validation, however, provides little assurance regarding the integrity of individual membranes within a production lot. Moreover, the test procedures and analysis can be difficult and complex. Flow based tests such as the liquid-liquid porometry test and the bubble point test do not provide a direct universal measurement of membrane retentive performance, but instead assess performance based on a correlation between integrity testing data, e.g. gas or liquid diffusion, and membrane retentive performance. Some flow based tests are also limited in their sensitivity, e.g. size detection limit of membrane defects. Additionally flow based tests are limited to single layer membrane devices, thus defects which are present in only one layer of a multi-layered device will not be detectable using these tests.
A need therefore exists for an integrity test that is suitable for any porous material, including, for example, both single layered and multi-layered devices, e.g. devices comprised of membranes and which provides a non-correlative, universal standard for assessing material performance. The test should be fast, sensitive, non-destructive, inexpensive and easy to execute. It would also be useful to be able to characterize a defect, e.g. by size or density, to determine if a desired performance criteria of the porous material has been compromised as a result of the defect or if the defect is inconsequential in terms of performance criteria. A need also exists for a device and system which can implement such a test.